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1/36. Clinical and radiographic response in three children with recurrent malignant cerebral tumors with high-dose tamoxifen.

    The purpose of this study was to deliver tamoxifen as antiangiogenic therapy to children with recurrent progressive malignant brain tumors. tamoxifen was administered orally in very high dosage to one child as monotherapy and to two children in combination with oral etoposide and dexamethasone. One boy was diagnosed with high-grade astrocytoma in the brain stem, one girl with anaplastic ependymoma of the fourth ventricule, and one girl with high-grade astrocytoma in the midbrain. Conventional treatment with multiple surgeries, first- and second-line chemotherapy, and external beam therapy had failed. Tumor reduction was seen in radiographic images together with clinical improvement in 2 children, and clinical and radiographic halting of tumor progression was demonstrated in the patient with anaplastic ependymoma. None of the patients developed complications from the treatment. Follow up of the patients ranged from 15 to 30 months with a mean of 17 months. These encouraging preliminary results suggest a potential for this type of therapy. More studies are needed to start clinical trials and prove that angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.
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2/36. Identifying differentially expressed genes associated with metastasis of follicular thyroid cancer by cDNA expression array.

    patients with follicular thyroid carcinoma have a higher incidence of metastasis than papillary thyroid carcinoma when thyroid cancer is diagnosed. The cDNA expression array technology is utilized herein to profile differentially expressed genes from metastatic human follicular thyroid carcinoma and reveal new tumor markers as well as target genes for therapeutic intervention. Tissue samples were obtained during surgical resection of the thyroid follicular carcinoma and metastatic tissue in the brain of the same patient. Two identical Atlas human cDNA expression arrays were hybridized with 32P-labeled cDNA probes derived from rna of either primary thyroid cancer or metastatic tissue. Parallel analysis of the hybridized signals allowed us to identify the alteration of gene expression in the metastasis process. Eighteen genes significantly overexpressed and 40 genes significantly underexpressed were identified in the metastatic thyroid cancer. genes that displayed an altered expression were associated with the processes of cell cycle regulation, apoptosis, dna damage response, angiogenesis, cell adhesion and mobility, invasion, and immune response. An expression profile of genes that are associated with metastasis process of follicular thyroid cancer was also discussed. Further investigation is required to understand the precise relationship between the altered expression of these genes and the metastasis process of follicular thyroid cancer.
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3/36. life-threatening giant mediastinal goiter: a surgical challenge.

    Mediastinal goiter is a well known benign disease, usually resectable through a cervical approach with minimal morbidity and mortality. Only occasionally a median sternotomy or a lateral thoracotomy may be required. The present case is worthy of presentation because of the exceptional dimension of the disease and the surgical challenge that it presented. In a 72-year-old woman a large intrathoracic goiter of the right thorax caused a severe dyspnoea due to an important contralateral mediastinal shift with compression of the lung, superior vena cava system and trachea. At surgical exploration, through a cervico-sternotomic approach, the mediastinal structures dislocation and the strong adherences between the anomalous neovascularized capsula of the mass and the surrounding structures, complicated the surgical dissection. An accidental lesion of the innominate artery required its reimplantation on the ascending aorta. An immense mass, was finally removed and pathological examination revealed a rare case of neovascularized, pseudosarcomatoid capsula among a benign hyperplastic proliferation. In spite of its benign nature, a giant goiter caused a life-threatening compression of the respiratory tract and lung parenchyma in this patient. The dimension of the lesions, the mediastinal anatomy alterations and the severe intraoperative haemorrhage represented major technical difficulties during surgical resection.
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keywords = haemorrhage
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4/36. Neuropathology of occipital horn syndrome.

    Occipital horn syndrome, formerly known as ehlers-danlos syndrome type IX or X-linked cutis laxa, is an allelic variant of Menkes' syndrome. Although the clinical symptomatology and systemic pathology findings have been well described in occipital horn syndrome, the neuropathology has not previously been reported. A kindred affected by the X-linked occipital horn syndrome is followed at the University of alabama at Birmingham. A severely mentally retarded dysmorphic man, who died at the age of 26 years, never gained the ability to walk or talk. Among other findings at autopsy, the patient had the skeletal anomalies previously described with occipital horn syndrome. Neuropathologic findings included neovascularization and extreme reduplication of the cerebral arteries, in conjunction with cystic medial degeneration; bilateral cerebellar hypoplasia; focal cortical dysplasia, and cerebellar heterotopias. These findings are similar to those seen in the brains of patients with Menkes' syndrome, which is not surprising, given the known phenotypic overlap and the proven allelism of occipital horn syndrome with classic Menkes' syndrome.
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5/36. A preliminary study of angiogenesis in paediatric glioblastoma multiforme and its correlation with survival.

    OBJECTS: There is a distinct challenge in bringing modern insights into glial tumour genesis to bear on improved outcomes for patients. Insights provided by neuroncological, neuroradiological, neuropathological, and neurosurgical investigations may offer significant advantages in the management of paediatric GBM. The goal of this study was to evaluate angiogenesis as a potential indicator of survival in paediatric glioblastoma multiforme (GBM). methods: Angiogenesis was evaluated in six cases of paediatric GBM with multiple criteria, including contrast enhancement on preoperative CT scan, histological vascular hyperplasia (VH) and endothelial proliferation (EP) and immunohistochemical tenascin-C (TN-C) expression. We employed a semiquantitative scale, ranging from not detected (zero) to marked ( 3), for each investigational parameter. We evaluated the influence of angiogenesis on survival in each case. CONCLUSIONS: In this preliminary study, angiogenesis provided information that correlated with survival, albeit in a limited number of patients. As we gain better understanding of the molecular biology of brain tumours, with the multitude of genetic alterations and growth factors new therapeutic approaches may emerge, which may hold the promise for cure.
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6/36. Intracerebral hemorrhage associated with Sneddon's syndrome: is ischemia-related angiogenesis the cause? Case report and review of the literature.

    Sneddon's syndrome is characterized by livedo reticularis and multiple ischemic infarcts often associated with antiphospholipid antibodies. Intracerebral hemorrhage (ICH) is unusual in Sneddon's syndrome and has not been reported as the presenting complaint. We report a 38-year-old woman with a history of two miscarriages, Raynaud's phenomenon and livedo reticularis who presented acutely with ICH. Angiography showed prominent leptomeningeal and transdural anastomoses (pseudoangiomatosis). Anticardiolipin antibodies were positive. A right frontal brain biopsy failed to reveal vasculitis and a skin biopsy was nonspecific. MRI showed residual intracerebral hemorrhage (ICH), diffuse atrophy, multiple small white matter infarcts and leptomeningeal enhancement. This is the first report of Sneddon's syndrome presenting with an ICH. It shares features with the Divry-van Bogaert syndrome. We discuss the cause of the pseudoangiomatosis pattern and its role in the genesis of the hemorrhage and suggest that cerebral angiography should be done in every patient with Sneddon's syndrome, as it could impact therapy.
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keywords = brain
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7/36. Topically applied minoxidil may cause fetal malformation: a case report.

    BACKGROUND: minoxidil is a K( ) channel opener able to cause relaxation of vascular smooth muscles and modify cell growth and cell fate or migration. It is now widely used for its hair growth promoting effects. When locally applied, it is absorbed through the skin and may have systemic pharmacological effects. CASE: A 28-year-old white pregnant woman daily applied minoxidil 2% to her scalp because of hair loss. At the 22nd gestational week, after a routine ultrasound test showing significant brain, heart, and vascular malformations of the fetus, pregnancy was interrupted. The placenta had numerous ischemic areas and a discrepancy between gestational age and villi maturation. In the villi, capillaries were increased in number, significantly enlarged, and excessively marginalized. The fetus' heart was increased in volume and had a globose shape, the aorta had a distal stenosis. The sigmoid colon was significantly increased in length and a mesentery commune was present. The brain had enlarged ventricles and abundant hemorrhages. Histological examination showed areas of demyelinization with gliosis, signs of excessive and inappropriate angiogenesis, and capillary rearrangement. CONCLUSIONS: Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women.
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8/36. Spontaneous development of bilateral subdural hematomas in an infant with benign infantile hydrocephalus: color Doppler assessment of vessels traversing extra-axial spaces.

    We present an infant with macrocrania, who initially demonstrated prominent extra-axial fluid collections on sonography of the brain, compatible with benign infantile hydrocephalus (BIH). Because of increasing macrocrania, a follow-up sonogram of the brain was performed; it revealed progressive enlargement of the extra-axial spaces, which now had echogenic debris. color Doppler US showed bridging veins traversing these extra-axial spaces, so it was initially thought that these spaces were subarachnoid in nature (positive cortical vein sign). However, an arachnoid membrane was identified superior to the cortex, and there was compression of true cortical vessels beneath this dural membrane. An MRI of the brain showed the extra-axial spaces to represent bilateral subdural hematomas. The pathogenesis of spontaneous development of the subdural hematomas, in the setting of BIH, is discussed. We also emphasize that visualizing traversing bridging veins through extra-axial spaces does not necessarily imply that these spaces are subarachnoid in origin.
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9/36. Gliomatosis cerebri: quantitative proof of vessel recruitment by cooptation instead of angiogenesis.

    OBJECT: Gliomas are the most common primary brain tumors, many of which (especially astrocytic and oligodendroglial neoplasms) are characterized by diffuse infiltrative growth in the preexisting brain tissue. Gliomatosis cerebri is a rare glial tumor and represents an extreme example of such diffuse infiltrative growth. This growth pattern not only hampers curative treatment but also allows for vessel cooptation rather than tumor angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of this study was to establish the extent to which tumor angiogenesis occurs in gliomatosis cerebri. methods: Computerized image analysis was performed to assess quantitatively two microvascular parameters (vessel density and diameter) in different areas of a brain harboring a gliomatosis cerebri. These regions were the cerebral white and gray matter in which there was a diffuse infiltrative tumor, cerebral white and gray matter in which there was a more compact growth pattern of tumor cells, and normal cerebral white and gray matter. In addition, the authors performed immunohistochemical stainings for blood-brain barrier (BBB) characteristics (Glut-1 and PgP) on samples obtained in these different areas. The results of the quantitative analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis was completely absent, a finding that is corroborated by the fact that the microvasculature in gliomatosis cerebri persists in exhibiting immunohistochemical characteristics of the BBB. CONCLUSIONS: The results of this study may help resolve the difficulties in radiological detection and delineation of the diffuse infiltrative part of glial brain tumors and put the expectations for antiangiogenic treatment of such tumors into perspective.
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10/36. Enhancing gliotic cyst wall with microvascular proliferation adjacent to a meningioma.

    Cystic meningiomas are uncommon. Contrast enhancement of the cyst wall of peritumoral cysts on radiological imaging is generally thought to indicate that the wall contains tumor cells. The authors present a patient with a peritumoral cyst that enhanced despite the absence of tumor cells. Histological analysis demonstrated a gliotic cyst wall with numerous microvascular proliferations (MVPs) adjacent to a mixed transitional and angiomatous/microcystic meningioma. Immunoreactivity for vascular endothelial growth factor (VEGF) and its receptor, flt-1, was observed in the endothelial cells of both intratumoral vessels and cyst wall MVPs. Immunoreactivity for tenascin-C was strongly observed within and around the vascular wall of MVPs and in gliotic tissue adjacent to the meningioma. These changes are unusual in the peritumoral brain parenchyma of a slow-growing convexity meningioma and the MVPs may account for the atypical contrast enhancement of the cyst wall despite the absence of tumor cells.
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